Antibiotic Update 2015: Disclosures Antibiotic Update 2015 No Financial Conflicts of Interest Shireesha Dhanireddy, MD 23 April 2015 Current Concepts in Drug Therapy Antibiotic Update 2015: Outline Cystitis / UTI Rhinosinusitis Skin & Soft Tissue Infections Case 1 I think I have a UTI A 21 year-old woman c/o increased urinary frequency & burning with voids. Recently became sexually active for the first time, uses diaphragm. No PMH, meds, or allergies. Afebrile. Modest suprapubic TTP. U/A: Many WBCs, moderate bacteria, few epis. SpGr 1.020 / ph 5 / +LE / +Nitrite Working Diagnosis: Acute uncomplicated bacterial cystitis 1
2011 IDSA Uncomplicated UTI Guidelines Antibiotic Update 2015: UTI Abx: Nitrofurantoin (Macrobid) 100mg PO BID x 5 days (avoid in pyelo!) OR TMP/SMX (Bactrim) <20%: 1 DS PO BID x 3 days OR Fosfomycin(Monurol) 3gm PO x 1 dose (avoid in pyelo!) TMP/SMX >20%: Cipro 500mg PO QD x 3 days OR Cefpodoxime 100mg PO BID x 7 days Fosfomycin 3 gm sachet in 32 oz H2O x 1 dose Comparable efficacy to FQ BUT bad choice for pyelo, and higher incidence of AE (headache, diarrhea) CID 1999;29:745 58 Antibiotic Update 2015: UTI Cipro vs. Cefpodoxime: Women with acute cystits randomized to 3 days of cipro vs cefopdoxime, f/u = 1 month. Outcome Cipro (n=150) Cefpodoxime (n=150) 95% CI Clinical Cure 83% 71% 3%-21% Micro Cure 96% 81% 8%-23% Vaginal E.coli colonization 16% 40% Hooton JAMA 2012 2
Antibiotics Update 2015: UTI Cipro vs. Cefpodoxime: Women with acute cystits randomized to 3 days of cipro vs cefopdoxime, f/u = 1 month. Cefpodoxime not noninferior to cipro. Caveat: Low dose & short course given! Suggestion: If cefpodox given, consider non-approved regimen: 200mg BID x 7 days. Antibiotic Update 2015: UTI The Future Pro-Biotics? Lactobacillus crispatus is normal vaginal flora, drives down ph, keeps E.coli at bay. Phase 2 trial of Lactin-V (Ocel) Suppositories (daily x 5, then weekly x 10) Outcome UTI Recurrence High Level Vaginal E.coli colonization L.crispatus (n=48) Placebo(n=4 8) Analysis 7/48 (15%) 13/48 (27%) RR 0.5 CI 0.2-2.1 RR 0.07 RR 1.1 P<0.01 Stapleton CID 2011 Antibiotic Update 2015: Case 2 A 28 year-old woman c/o 2 days of subjective fever, rhinorrhea, nasal congestion, sore tx, HA. I really want some antibiotics to get on top of this. Meds: None. PMH: None. SH: Smoker, no drug abuse. AVSS, boggy turbinates, modest facial pain, neck supple, lungs clear. PLAN: Decongestants, analgesics, call in a week if not better. Antibiotic Update 2015: Rhinosinusitis American adults have 2-3 / year ~98% viral (rhino, corona, paraflu, etc.) 2% bacterial (S.pneumo, H.flu, M.cat) Symptomatic relief indicated regardless of cause No ironclad symptoms or signs distinguish between viral & bacterial etiologies Single best predictor of bacterial involvement: symptoms > 10 days Meta-Analysis: NNT = 15 (Young Lancet 2008) 3
Antibiotic Update 2015: Rhinosinusitis Fundamentals Reassurance: Good news, no abx needed! Scheduled anti-inflammatory / analgesics Judicious decongestants in select cases Consider topical steroids if h/o allergy Vitamin C: A fine way to acidify your urine Appropriate hygiene and infection control! Antibiotic Update 2015: Rhinosinusitis ZINC Inhibits rhinovirus in vitro Oral zinc in Cochrane Meta-Analysis: 15 placebo-controlled trials 1,360 patients Treatment started within 24 hours of sx Antibiotic Update 2015: Rhinosinusitis ZINC Summary May reduce symptoms by about a day Duration of symptoms 0.97 days less May reduce antibiotic consumption OR 0.27 May lead to minor, temporary side effects OR 1.59; leading side effects: bad taste, nausea, constipation Singh Cochrane Rev 2011 Antibiotic Update 2015: Rhinosinusitis NETI POT Favorable Cochrane Meta Analysis Many patients adore it Advise filtered, boiled, distilled, or sterile water! 4
Abx Update 2012: Rhinosinusitis Warning Signs Persistent, high-grade fever (e.g. > 102 F) Altered Mental Status Dyspnea Ocular or orbital pain DKA Facial Erythema Thorough, rapid evaluation required antibiotics may be appropriate! Case Continued She took your advice No antibiotics were prescribed Zinc made food taste funny Ten days have elapsed She is no better! Sinus pain is worse, headaches have increased! Chaotic fever persists! Case Continued Which of the following will inform your choice of antibiotic? A) Cost? B) Allergies? C) Pregnancy? D) Drug interactions? E) Past abx? F) Local resistance? G) Past microbiology? H) Candida History? I) Sun exposure? J) Tendon rupture risk? K) Diarrhea history? BACTERIAL PATHOGENS IN ADULT RHINOSINUSITIS Pathogen Incidence (%) S.pneumoniae 41 H.influenzae 35 Anaerobes 7 Streptococci 7 M.catharralis 4 S.aureus 3 Other 4 5
Antibiotic Update 2015: Rhinosinusitis None proven superior Erythro base 500mg BID Amox/clav 875 BID Cefpodoxime 200 BID Cefdinir 600 QD Doxycycline 100 BID TMP/SMX 1 DS BID Levofloxacin 500 QD Moxifloxacin 400 QD Concern: Pneumococcal Resistance Antibiotic 2015: Rhinosinusitis First-Line Abx Amox/clav 875-2,000 BID x 5-7 days Second-Line Abx Doxycycline 100 BID or Levofloxacin 500 QD or Moxifloxacin 400 QD 5-7 days No Longer Recommended Azithromycin or TMP/SMX IDSA Gudielines April 2012 Antibiotic Update 2015: Case 3 My leg is killing me! 56 y/o diabetic man presents with red leg x 48 hours. No recalled trauma, no pus, no h/o MRSA, no household contacts with staph. Brawny erythema, macerated toe web spaces. Skin & Soft Tissue Infections 6
SSTI New Guidelines 2014 Purulent Management Differs for purulent vs non-purulent infections Stratified based on severity Purulent Telavancin Vancomycin or Daptomycin or Linezolid or Televancin or Ceftaroline Bactericidal lipoglycopeptide antibiotic with activity against MRSA and other Gram + bacteria Mechanism of action inhibits cell wall synthesis and disrupts bacterial membrane depolarization Approved for treatment of SSTI Also approved for treatment of HAP and VAP due to S. aureus Common/serious AE: Renal toxicity 7
Ceftaroline Anti-MRSA, 5 th generation cephalosporin Available IV only Approved for treatment of SSTI and CAP Cost: $82/day (vs ~$12/day for vancomycin Reserve for patients with proven MRSA, consult ID Tedizolid (Sivextro) FDA approved June 2014 for treatment of skin/soft tissue infections Dose: 200mg IV/PO daily x 6 days Mechanism of action: Same as linezolid (oxazolidinone) No dose adjustment for renal or hepatic impairment Precautions: Weak MAO inhibitory activity Cost: IV - $224 ; PO - $280 Linezolid IV - $90 ; PO - $237 Purulent Purulent MRSA TMP/SMX or doxycycline MSSA Nafcillin or Cefazolin or Clindamycin TMP/SMX or doxycycline 8
Purulent Purulent MRSA TMP/SMX NO ANTIBIOTICS MSSA Dicloxacillin or Cephalexin Nonpurulent Necrotizing Infection/Cellulitis/Erysipelas Emergent Surgical Debridement Vancomycin + Pip/Tazo IV Oral Hammond SP et al. N Engl J Med 2008 9
Nonpurulent Necrotizing Infection/Cellulitis/Erysipelas Monomicrobial Strep pyogenes PCN + Clinda Clostridium sp PCN + Clinda Vibro vulnificus Doxycycline + Ceftazidime Aeromonas hydrophila Doxycycline + Ciprofloxacin Nonpurulent Necrotizing Infection/Cellulitis/Erysipelas PCN or Ceftriaxone or Cefazolin or Clindamycin Emergent Surgical Debridement Polymicrobial Vancomycin + Pip/Tazo Vancomycin + Pip/Tazo IV Oral Emergent Surgical Debridement Vancomycin + Pip/Tazo IV Oral Nonpurulent Necrotizing Infection/Cellulitis/Erysipelas PCN VK or Cephalosporin or Dicloxacillin or Clindamycin New Options for SSTIs in 2015 Emergent Surgical Debridement Vancomycin + Pip/Tazo IV Oral 10
Dalbavancin Oritavancin Inhibits cell wall synthesis Active against Gram + bacteria (including MRSA) Long half life ~ 8.5 days, dosed once weekly Non-inferior to vancomycin Cost: $4500 / course Semisynthetic derivative of vancomycin Broad Gram + coverage, including MRSA Long half-life, ~10 days Non-inferior to vancomycin Cost: $3000 single dose Corey GR et al. N Engl J Med 2014 Antibiotic Update 2015: Summary Cystitis / UTI Consider local TMP/SMX resistance rate when determining empiric treatment Rhinosinusitis Amox/clav first line treatment Skin & Soft Tissue Infections New drugs available but their role unclear and cost may be prohibitive Thanks! Questions: sdhanir@uw.edu 11